FAM81A Identified as a Stemness-Related Gene by Screening DNA Methylation Sites Based on Machine Learning-Accessed Stemness in Pancreatic Cancer

Abstract

Aim: We thoroughly discuss the interaction between the stemness index and DNA methylation in pancreatic cancer (PC). Materials&methods: First, the stemness indices of PC (denoted mRNAsi and mDNAsi) were calculated using a one-class logistic regression machine-learning algorithm. Second, we screened the central methylation sites associated with stemness and screened out the key genes. We investigated the DNA methylation regulators associated with the key genes. Finally, using CIBERSORT and TIMER, we assessed the influence of stemness indexes and key genes on PC microenvironment formation. Results: In this study we quantified the stemness indices for PC and screened 20 related central DNA methylation sites. Further analysis of the methylation site cg22687244, located in the 3′ UTR, revealed that it promoted the expression of the key gene FAM81A. We show that FAM81A may be regulated by DNA methylation regulators. Furthermore, immune cells were found to be more abundant in PC microenvironments with high expression of FAM81A. Conclusion: We report for the first time that the 3′ UTR methylation of FAM81A is closely related to PC stemness and contributes to tumor immune infiltration. Therefore FAM81A may serve as a potential marker to guide the treatment of PC.

Keywords::

• DNA methylation
• machine learning
• pancreatic cancer
• prognosis
• tumor immunity
• WGCNA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0098

Author contributions

Q Zhang: substantial contributions to the conception or design of the work; analysis, interpretation of data for the work; drafting the work. S Sun and Q Xie: analysis of data for the work. J Yao, X Wang and J Qian: revising the manuscript critically for important intellectual content. Z Li: final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments

the authors want to thank C Xin for her great support of our research.

Financial&competing interests disclosure

This work was supported by a grant from the National Natural Science Foundation of China (No. 81772516). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing assistance was provided by MJEditor in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81772516). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.